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Synthesis and characterization of new copper- and zinc-chloroquine complexes and their activities on respiratory burst of polymorphonuclear leukocytes

Abstract:

The metal-chloroquine (CQ) complexes, Cu(CQ)2Cl (1), Cu(CQ)(PPh3)(NO3) (2), [Cu(OAc)2(CQ)] 2 (3) ZnCl2(CQ)(H2O)2 (4), [Zn(OAc)2(CQ)(H2O)]2 (5), were synthesized and characterized by NMR, FAB-mass, elemental analysis, and UV-Vis, EPR and IR spectroscopies. The effects of these compounds on the generation of reactive oxygen species (ROS) from human neutrophils (PMNs) were tested in the concentration range 1-100 μM and compared to that of chloroquine. The data show that the copper-chloroquine complexes 1-3 inhibit neutrophil release of ROS in PMNs activated either by a phorbol ester or by phagocytosable particles. Both effects were dose-dependent, with an IC50 of ∼10 μM. With the same stimulants, there was only modest inhibition of ROS generation by any of the zinc-chloroquine complexes 4-5 at 10-100 μM. All complexes did not show significant in vitro toxicity as assayed by the trypan blue exclusion method. Our results reinforce previous observations that many metal derivatives of anti-inflammatory drugs affect neutrophil functions with higher potency than their parent ligands. © 2005 Elsevier Inc. All rights reserved.